Exome Sequencing and MRI in Prenatal Diagnosis: A Case Report of Joubert Syndrome in Colombia

To report the prenatal diagnosis of CSPP1-related Joubert Syndrome 21 (JS21) in a fetus with multiple congenital anomalies, highlighting the complementary role of detailed neuroimaging and molecular genetic testing.

A fetus with suspected central nervous system anomalies underwent detailed prenatal ultrasound and fetal neurosonography, followed by magnetic resonance imaging (MRI) and exome sequencing. We reviewed prenatal imaging, molecular findings, and postnatal outcomes.

A 25-year-old G4P2011 patient with a history of adverse pregnancy outcomes associated with fetal malformations was referred at 32 weeks of gestation. Ultrasound findings included occipital meningocele, cerebellar vermis agenesis, and bilateral cleft lip and palate. Fetal MRI confirmed the characteristic molar tooth sign, raising suspicion of Joubert syndrome. Exome sequencing identified a homozygous canonical splice-site variant in CSPP1, NM_001382391.1:c.2968 + 1G > A (rs587777142), classified as pathogenic according to ACMG/AMP criteria. The pregnancy resulted in the birth of a female neonate weighing 3165 g, and postnatal clinical and imaging evaluation supported the prenatal diagnosis of CSPP1-related JS21.

This case illustrates the value of integrating detailed fetal neuroimaging with molecular genetic testing for the prenatal diagnosis of Joubert syndrome. Recognition of characteristic imaging findings can guide targeted interpretation of genetic results, allowing earlier diagnosis, more accurate counseling, and coordinated prenatal and postnatal care.